Ceprova - instructions for use, doses, side effects, contraindications

Antimicrobial preparation of a broad spectrum of action from the group of fluoroquinolones. The drug inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling the chromosomal DNA around the nuclear RNA, which is necessary for reading the genetic information), violates DNA synthesis, growth and division of bacteria; causes significant morphological changes (including the cell wall and membranes) and the rapid death of the bacterial cell. Ciprofloxacin acts bactericidal both on gram-negative microorganisms, multiplying, and on being in a resting phase, (since it affects not only the DNA-gyre, but also causes lysis of the cell wall). On Gram-positive microorganisms - only in the period of division.The low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. While receiving ciprofloxacin occurs parallel generating resistance to other antibiotics, does not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria which are resistant, such as aminoglycosides, penicillins, cephalosporins, tetracyclines.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens: Legionella pneumophila, Brucella spp .. Chlamydia trachomatis. Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.

Gram-positive aerobic bacteria are also sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin.

Sensitivity of bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (to suppress them, high concentrations are required).

To the drug are resistant: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides, Corynebacterium diphtheriae.

He is effective against Treponema pallidum.

Resistance develops very slowly, because on the one hand, after the action of ciprofloxacin are left with persistent microorganisms, and on the other - the bacterial cells do not have the enzymes that inactivate it. There is no cross-resistance with penicillins, cephalosporins, aminoglycosides.

Pharmacokinetics:

After an intravenous (IV infusion) of 200 mg or 400 mg, the time to reach the maximum plasma concentration is 60 minutes, the maximum concentration is 2.1 μg / ml and 4.6 μg / ml, respectively. The volume of distribution is 2-3 l / kg, the connection with plasma proteins is 20-40%.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). Concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal and pelvic organs, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary organs, lung tissue, bone tissue , muscles, synovial fluid and articular cartilage, peritoneal fluid, skin.The cerebrospinal fluid penetrates in a small amount, where its concentration in uninflated cerebral membranes is 6-10% of that in the serum, and when inflamed - 14-37%. Ciprofloxacin also well penetrates into the eye fluid, bronchial secretion, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

Metabolised in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin).

The half-life is 5-6 hours with intravenous administration, and with chronic renal insufficiency up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion in unchanged form - 50-70% and in the form of metabolites - 10%, the rest - through the gastrointestinal tract: A small amount is excreted in breast milk. After intravenous administration, the concentration in the urine during the first 2 hours after administration is almost 100 times greater than in the serum, which significantly exceeds the minimum inhibitory concentrations (MICs) for most pathogens of urinary tract infections.

Kidney clearance - 3-5 ml / min / kg; total clearance - 8-10 ml / min / kg.

In chronic renal insufficiency (creatinine clearance above 20 ml / min), the percentage of the drug withdrawn through the kidneys decreases, but cumulation in the body does not occur due to a compensatory increase in the metabolism of the drug and excretion through the gastrointestinal tract.

Indications:

Bacterial infections caused by susceptible microorganisms:

- Diseases of the lower respiratory tract (acute and chronic (at the stage of exacerbation) bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis);

- Infections of ENT organs (acute sinusitis);

- Infections of the kidneys and urinary tract (cystitis, pyelonephritis);

- Complicated intra-abdominal infections (in combination with metronidazole), incl. peritonitis;

- Chronic bacterial prostatitis;

- Uncomplicated gonorrhea;

- Typhoid fever, campylobacteriosis, shigellosis, diarrhea of "travelers";

- Infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);

- Bones and joints (osteomyelitis, septic arthritis);

- Septicemia;

- Infections against the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia);

- Prevention of infections during surgical interventions;

- Prevention and treatment of pulmonary form of anthrax.

Application in children:

Therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years, for the prevention and treatment of pulmonary form of anthrax (infection Bacillus anthracis).

Contraindications:

Hypersensitivity to fluoroquinolones, deficiency of glucose-6-phosphate dehydrogenase, children and adolescence (up to 18 years - until the completion of the formation of the skeleton, in addition to the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years, prevention and treatment of pulmonary form of anthrax (infection Bacillus anthracis)), pregnancy, lactation, simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness).

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, marked renal and / or hepatic insufficiency, tendon damage with previous treatment with fluoroquinolones, elderly age.

Dosing and Administration:

Ciprofloxacin is administered as an intravenous infusion lasting at least 30 minutes (200 mg) and 60 minutes (400 mg).The dose of ciprofloxacin depends on the severity of the disease, the type of infection, the body's condition, age, weight and kidney function in the patient.

Infusion solutions ready for use can be mixed with 0.9% NaCl solution, Ringer's and Ringer's lactate solution, 5 and 10% dextrose solution, 10% fructose solution, and also a solution containing 5% dextrose solution with 0.225-0, 45 % NaCl solution.

In infections of the lower respiratory tract: 200-400 mg 2 times a day;

With infections of the urinary tract: acute uncomplicated - 100 mg 2 times a day; cystitis in women (before menopause) - once 100 mg; Complicated - 200 mg 2 times a day;

With uncomplicated gonorrhea: 100 mg once, with extragenital - 100 mg 2 times a day;

Infectious diarrhea: 200 mg 2 times, the course of treatment - 5-7 days;

Especially severe infections (streptococcal pneumonia, infectious complications of cystic fibrosis, infections of bones and joints, septicemia, peritonitis), especially caused Pseudomonas, Staphylococcus - 400 mg 3 times a day;

Pulmonary form of anthrax (treatment and prevention): 400 mg twice a day;

For the prevention of infections during surgical interventions: 200-400 mg for 0.5-1 h before the operation; when the duration of the operation is more than 4 hours, re-injected at the same dose; With other infections (depending on the severity of the course): 200-400 mg 2 times a day. Older patients are prescribed lower doses, depending on the severity of the infection and the creatinine clearance rate.

In pediatrics:

In the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years: 10 mg / kg 3 times a day (maximum dose of 1200 mg). Duration of treatment: 10-14 days.

With pulmonary form of anthrax (prevention and treatment): 10 mg / kg 2 times a day. The maximum single dose is 400 mg, the daily dose is 800 mg. The total duration of taking ciprofloxacin is 60 days.

In chronic renal failure: with a creatinine clearance of 31-60 ml / min / 1.73 square meters or a serum creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum daily dose of 800 mg. When creatinine clearance is less than 30 ml / min / 1.73 m2 or serum creatinine concentration is above 2 mg / 100 ml and during hemodialysis the maximum daily dose is 400 mg; in hemodialysis ciprofloxacin injected after a hemodialysis session.

With peritoneal dialysis, the infusion solution is added to the dialysate (inside the peritoneal) at a dose of 50 mg per liter of dialysate 4 times a day (every 6 hours).

The average course of treatment: 1 day - with acute uncomplicated gonorrhea and cystitis; up to 7 days - with infections of the kidneys, urinary tract and abdominal cavity, during the entire neutropenic phase - in patients with weakened body defenses, but no more than 2 months - with osteomyelitis and 7-14 days - with all other infections. With streptococcal infections due to the danger of late complications, treatment should last at least 10 days. In patients with immunodeficiency treatment is carried out throughout the neutropenia period.

Treatment should be conducted for at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

After IV application, you can continue treatment orally.

Side effects:

Co side of the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite, cholestatic jaundice (especially in patients with liver disease), hepatitis, hepatonecrosis.

From the urinary system: hematuria, crystalluria (especially in alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen function, interstitial nephritis.

From the central nervous system: dizziness, headache, fatigue, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), sweating, increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can do harm to himself), migraine, fainting, thrombosis of the cerebral arteries.

From the sense organs: violation of taste and smell, visual impairment (diplopia, change in color perception), tinnitus, hearing loss.

From the cardiovascular system: tachycardia, heart rhythm disturbances, lowering blood pressure.

From the hematopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia.

From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia.

Laboratory indicators: hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Allergic reactions: dermal itching, urticaria, the formation of blisters accompanied by bleeding, and small nodules that form scabs, drug fever, puncture of the face or larynx, dyspnea, eosinophilia, vasculitis, nodal erythema, exudative erythema multiforme (v. Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Local reactions: pain and burning at the injection site, phlebitis.

Other: general weakness, superinfection (candidiasis, pseudomembranous colitis), increased photosensitivity, "tides" of blood to the face.

Overdose:

The specific antidote is unknown. It is necessary to carefully monitor the patient's condition, to carry out usual emergency measures, to ensure sufficient fluid intake. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

Due to the decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and prolongs the half-life of theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and decreases the prothrombin index.

Simultaneous reception with tizanidine increases the maximum plasma concentration of the latter 7-fold (4 to 21 times) and AUC 10-fold (6 to 24 times), which increases the risk of pronounced reduction in blood pressure and drowsiness.

When combined with other antimicrobial agents (beta-lactam antibiotics, aminoglycosides, vancomycin, clindamycin, metronidazole) the activity of ciprofloxacin increases. It can be successfully applied in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp., with mezlocillin, azlocillin and other beta-lactam antibiotics - with streptococcal infections; with isoxazolylpenicillins and vancomycin - with staphylococcal infections; with metronidazole and clindamycin in anaerobic infections.

Strengthens the effect of warfarin and other indirect anticoagulants, prolonging the time of bleeding.

Increases the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine. Such patients need control of this indicator 2 times a week.

Nonsteroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures.

Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration in the plasma.

Joint appointment of uricosuric drugs leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Probenecid increases the concentration in the blood.

Drugs alkalinizing urine (citrates, sodium bicarbonate, inhibitors of carbonic anhydrase), reduce solubility (the probability of crystalluria increases).

With simultaneous reception increases the effect of indirect anticoagulants.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable under acidic conditions (the pH of the infusion solution of ciprofloxacin is 3.9-4.5). Do not mix the IV solution with solutions having a pH of more than 7.

Special instructions:

Ciprofloxacin is not a drug of choice in suspected or established pneumonia caused by Streptococcus pneumoniae.

If a severe and prolonged diarrhea occurs during or after treatment with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

If pain occurs in tendons or when the first signs of tendovaginitis appear, treatment should be discontinued (individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones are described).

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake and maintenance of acid urine reaction are also necessary.

Patients with epilepsy, seizures in the anamnesis, vascular diseases and organic brain damage, in connection with the threat of development of adverse reactions from the central nervous system ciprofloxacin should be

With simultaneous intravenous administration of ciprofloxacin and drugs for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the heart rate, blood pressure, and electrocardiogram is necessary.

During the treatment period, direct exposure to ultraviolet light should be avoided.

Effect on the ability to drive transp. cf. and fur:

Patients receiving ciprofloxacin, one should refrain from engaging in potentially dangerous activities,requiring increased attention and speed of mental and motor reactions.

Form release / dosage:

Solution for infusion, 2 mg / ml.

Packaging:

To 100 ml in sterile hermetically sealed bottles of low-density polyethylene. A label is attached to the bottle. The bottle is placed in a polypropylene bag, then in a cardboard box together with the instruction for use.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015058 / 01

Date of registration:30.06.2009

The owner of the registration certificate:Lupine Co., Ltd.Lupine Co., Ltd. India

Manufacturer: & nbsp

LUPIN, Ltd. India

Representation: & nbspLUPIN LIMITEDLUPIN LIMITED

Information update date: & nbsp22.10.2015

Illustrated instructions

Instructions

Ceprova (Ceprova)